Nordic Congres of Clinical Neurophysiology
Transcription
Nordic Congres of Clinical Neurophysiology
Nordic Congres of Clinical Neurophysiology 7-9th of May 2015 Hotel Marienlyst, Helsingør, Denmark Webside: www.nccn2015.dk Scientific programme Thursday May 7th 09:00 – 17:30 Registration 10:00 – 11:00 Coffee in the exhibition area 11:00 – 11:05 Welcome 11:05 – 12:30 New neurophysiological methods in epilepsy Chairmen; Martin Fabricius, Department of Clinical Neurophysiology, Rigshospitalet, Denmark Sandor Beniczky, Department of Clinical Neurophysiology, Filadelfia, Denmark 11:05 - 11:10 Introduction (chairmen) 11:10 – 11:30 Stereo-EEG: The Göteborg experience. David Krýsl, Sahlgrenska University Hospital, Gothenburg, Sweden. 11:30 - 11:45 EEG – source imaging in Epilepsy. Göran Lantz, Neurology Clinic, University Hospital, Geneva, Switzerland and Lund University Hospital, Sweden 11:45 - 12:00 MEG – source imaging. Sandor Beniczky, Department of Clinical Neurophysiology, Filadelfia, Denmark 12:00 - 12:10 Source imaging, discussion. 12:10 - 12:30 ContinuousEEG. Martin Fabricius, Department of Clinical Neurophysiology, Rigshospitalet, Denmark 12:30 – 14:00 Lunch, coffee in the exhibition area and poster session 1 14:00 – 15:30 Channelopathies and neurophysiological investigations Chairman; Christian Krarup, Department of Clinical Neurophysiology, Rigshospitalet, Denmark. 14:00 - 14:30 Channelopathies in peripheral nerve. Christian Krarup, Department of Clinical Neurophysiology, Rigshospitalet, Denmark 14:30 - 15:00 Channelopathies in muscle. Werner Z’Graggen, Universitätsklinik für Neurochirurgie, Bern Universty Hospital, Switzerland 15:00 - 15:30 Channelopathies in pain. Kristin Ørstavik, Section of Clinical Neurophysiology, department of neurology, Oslo University Hospital, Norway 15:30 – 16:00 Coffee in exhibition area 16:00 – 17:30 Free communications 17:45 Meet in the hotel lobby 18:00 Welcome reception at Kronborg with guided walk. Friday May 8th 08:30 – 17:00 Registration 09:00 – 10:00 Keynote lecture; Single fiber EMG – historical landmarks and present developments. Erik Stålberg, Institute of Neuroscience, Clinical Neurophysiology, Uppsala, Sweden 10:00 – 10:20 Coffee in exhibition area 10:20 – 11:50 Neuromuscular investigation in the critically ill patient Chairman; Clarissa Crone, department of Clinical Neurophysiology, Rigshospitalet, Denmark. 10:20 - 10:50 Critical illness myopathy/polyneuropathy: Pathophysiology and diagnostic procedures during early course and follow up Susanne Koch, Department of Anesthesiology and Intensive Care Medicine, Charité Campus VirchowKlinikum, Berlin, Germany. 2 10:50 - 11:20 Bench to bedside project on intensive care unit muscle wasting: Underlying mechanisms and specific interventions. Lars Larsson, Department of Physiology & Pharmacology, Dept. of Clinical Neuroscience, Karolinska Institute, Sweden 11:20 - 11:50 Optimizing testing methods and collection of reference data for differentiating critical illness polyneuropathy from critical illness myopathy: Humberto Skott, Department of Physiology & Pharmacology, Dept. of Clinical Neuroscience, Karolinska Institute, Sweden 11:50 – 13:10 Lunch, coffee in the exhibition area and poster session 13:10 – 14:30 Neurophysiological methods for intraoperative monitoring Chairman; Birger Johnsen, Department of Clinical Neurophysiology, Aarhus University Hospital, Denmark. 13:10 - 13:30 IOM in glioma surgery: Hans Axelson, Department of Clinical Neurophysiology, Uppsala University Hospital, Sweden 13:30 - 13:50 IOM in brainstem surgery: Pål Gunnar Larsson, Division of Surgery and Clinical Neuroscience, Oslo University Hospital, Norway 13:50 - 14:10 Intraoperative neurophysiology in intraspinal surgery: Jonas Persson, Department of Clinical Neurophysiology, Karolinska University Hospital, Stockholm,Sweden 14:10 - 14:30 Intraoperative monitoring of scoliosis surgery. Ralf-Peter Michler, Department of Clinical Neurophysiology, St. Olav’s Hospital, University Hospital of Trondheim, Norway 14:30 – 15:00 Coffee in exhibition area 15:00 – 16:00 Nerve and muscle Ultrasound and MRI Chairmen; Erisela Qerama Montvilas, Department of Clinical Neurophysiology, Aarhus University Hospital,Denmark 3 Nils Wolfram, Department of Clinical Neurophysiology, Glostrup, Denmark 15:00 - 15:20 What can you see on neuromuscular imaging? Michel Court Payen, Gildhøj Private Hospital, Denmark 15:20 - 15:40 Nerve and muscle ultrasound in neuromuscular disorders - Experiences and results of prospective studies: Erisela Qerama Montvilas, Department of Clinical Neurophysiology, Aarhus University Hospital, Denmark 15:40 - 16:00 Experiences of combined electrophysiology and High Resolution UltraSound in the examination of peripheral nerves: Nils Wolfram and Janus Kaufmann, Department of Clinical neurophysiology, Glostrup, Denmark 16:00 – 17:00 Parallel hands-on sessions: 1) Neuromuscular ultrasound. Nils Wolfram, Erisela Qerama 2) Threshold tracking in channelopathies. M. Moldovan, W. Z’Graggen, H. Tankisi 19:00 Gala dinner Saturday May 9th 08:30 – 11:00 Registration 09:00 – 10:00 Keynote lecture; Brain basis of social interaction. Riitta Hari, Brain Research Unit, Aalto University, Finland 10:00 – 10:30 Coffee in exhibition area 10:30 – 12:30 Neurophysiological methods in sleep and aging Chairman; Benedikte Wanscher, Department of Clinical Neurophysiology, Glostrup, Denmark 10:30 - 10:45 REM sleep Behaviour Disorder: An early sleep disease marker for late neurodedeneration. Poul Jennum, Department of Clinical Neurophysiology, Glostrup, Denmark 4 10:45 - 11:00 Electromyographic activity in REM sleep behavior disorder. Rune Frandsen, Department of Clinical Neurophysiology, Glostrup, Denmark 11:00 - 11:15 Prepulse inhibition is associated with attention, processing speed, and 123I-FP-CIT SPECT in Parkinson’s disease. Marielle Zoetmulder, Department of Clinical Neurophysiology, Glostrup, Denmark Denmark 11:15 - 11:30 Sleep stability and transitions in patients with idiopathic REM sleep behaviour disorder and patients with Parkinson ’s disease. Julie AE Christensen, Department of Clinical Neurophysiology, Glostrup, Denmark 11:30 - 11:45 The Copenhagen longitudinal study of male cognitive aging and fMRI and EEG measures of cognitive decline. Martin Lauritzen, Department of Clinical Neurophysiology, Glostrup, Denmark 11:45 - 12:00 Selective attention modules auditory and visual steady state responses. Krisztina Benedek, Department of Clinical Neurophysiology, Glostrup, Denmark 12:00 - 12:15 Neurophysiological correlates of illusions: Visual perceptive network study. Anna Horwitz, Department of Clinical Neurophysiology, Glostrup, Denmark 12:15 – 12:30 Neocortical gamma oscillations in epilepsy. Krisztina Benedek, Department of Clinical Neurophysiology, Glostrup, Denmark 12:30 Sandwiches in exhibition area and goodbye 5 Stereo-EEG: the Göteborg experience David Krysl, Bertil Rydenhag, Kristina Malmgren Sahlgrenska University Hospital, Göteborg, Sweden Introduction: Stereoencephalography (SEEG) uses stereotactically implanted intracerebral electrodes to test hypotheses about origin and propagation of epileptic seizures. It allows exploration of deep cortical regions and reconstruction of seizure pattern in 3D. SEEG candidates are commonly MRnegative or have electroclinical syndrome discordant with lesion location. In Göteborg, SEEG was first performed in 2013/04 and is now important part of epilepsy surgery program. Methods: Review of approach to SEEG in Göteborg and presentation of patients investigated by SEEG since 2013/04. Results: 6 adults (age 20-40) and 4 children (age 4-9) underwent SEEG. 4 adults presented as TLE with concerns about extent of epileptogenic zone or multilobar (fronto-temporal) involvement. Two adults presented as frontal lobe epilepsy (FLE), one was later reclassified as possible medial parietal case. One child presented as TLE+ (TPO), and 3 as FLE. SEEG was well tolerated, no major complications were observed. Minor complications (without deficits) included one epidural hematoma caused by orthogonal frontoorbital electrode and one bleeding during electrode insertion. Reduction in number of electrodes due to poor bone quality was unexpectedly needed in the youngest child. SEEG lead to cortical resection in 3/4 children and 4/6 adults. All three operated children and 3/4 adults are seizure-free post-op (follow-up 0,5-1 year). Conclusions: SEEG is an effective and relatively safe method for investigating complicated patients with refractory focal epilepsy. Its successful use is heavily dependent on the comprehensiveness of preimplantation hypotheses. Its use is not limited to adults, but it may be technically difficult in small children. Given the complexity of patients referred for SEEG, short-term seizure freedom in 6/7 operated patients is encouraging. SEEG may also bring evidence in favor of conservative approach that helps to avoid unsuccessful attempts at resective surgery. BACK TO PROGRAM 6 EEG Source Imaging in Epilepsy Göran Lantz, Electrical Geodesic Inc, Eugene OR, USA In presurgical investigations of patients with pharmaco-resistant epilepsy different non-invasive investigations are performed before proceeding to either invasive recordings or directly to surgery. Among the different non-invasive techniques for localizing the epileptic focus are the electromagnetic methods (based on EEG or MEG recordings) and the hemodynamic methods (PET,SPECT,fMRI). These classes of investigations are complementary in the sense that the electromagnetic methods have a better temporal resolution (down to a few milliseconds) whereas the hemodynamic methods (notably fMRI) have a better spatial resolution. One such non-invasive technique for localizing the epileptic focus is Electrical Source Imaging (ESI). This technique is used to 3-dimensionally localize the source of interictal epileptiform activity from high density EEG recordings. In this presentation a workflow for the ESI investigations will be suggested. The importance of using a sufficient number of recording electrodes as well as the importance of which timepoint of the spike is chosen for the analysis will be demonstrated. Different evaluation studies demonstrating the usefulness of the technique will be presented and the possibility to combine ESI with other non-invasive neuroimaging techniques will be discussed. BACK TO PROGRAM 7 MEG – source imaging Sandor Beniczky (Danish Epilepsy Centre and Aarhus University) Several strategies are available for solving the inverse solution: determining the location in the brain of the cortical areas generating EEG and/or MEG signals. This presentation reviews the principles behind the various source imaging strategies and reviews the published evidence for the diagnostic accuracy and clinical utility. BACK TO PROGRAM 8 cEEG Martin Fabricius, dep.of Clinical Neurophysiology, Rigshospitalet, Copenhagen. Continuous EEG (cEEG) is a key instrument for diagnosing and treating non-convulcive seizures and nonconvulsive status epilepticus. Furthermore non-epileptic motor manifestasions are common in unconscious patients in the intensive care unit and may be distinguished from true seizures by means of cEEG. The analysis requires a considerable man-power from trained EEG-interpreters, but may be performed on-line by remote-access. The cEEG trace is evaluated by direct inspection as well as by means of quantitative EEG measures such as amplitude integrated EEG and power spectrum trend analysis. Bedside staff must be trained to enter events into the EEG software such as changes in medication and clinical events, to allow an optimal assessment. Current dialogue with the attending neurologists and intensivists is very important. Recordings will be presented to demonstrate typical cases as well as pitfalls. BACK TO PROGRAM 9 Channelopathies in peripheral nerve Christian Krarup, Department of Clinical Neurophysiology, Rigshospitalet and University of Copenhagen, Denmark Nerve fibre function is dependent on the concerted activation and inactivation of a number of ionchannels integrated in the axolemma. In myelinated fibres, the different channels are segregated at the node of Ranvier and at the internode. The homeostasis of ion concentrations is furthermore dependent on various ion pumps and exchangers that maintain the axon membrane potential. Abnormalities of ion channels and pump function may cause cramps, paraesthesia, pain, sensory loss or weakness and may eventually lead to nerve fibre degeneration. Channelopathies may be hereditary or acquired. Hereditary channelopathies may affect Na + or K+ channels and include symptoms localized to the peripheral or the central nervous system or both. Acquired disorders that affect ion channels directly by blocking or indirectly through metabolic changes are more common, as for example autoimmune blocking of K +-channels in motor fibres. Furthermore, changes in ion-channel distribution may have functional implications in for example chronic demyelinating neuropathies and in regenerated fibres. Studies in hereditary motor and sensory neuropathies have also shown that aberrant ion-channels, usually not present at the node of Ranvier, may become expressed, and such ectopic channels may cause disturbed function confirming that transcriptional changes may lead to channelopathies. Conventional nerve conduction studies are not well suited to unravel changes in function associated with ion-channel or axon membrane dysfunction. NCS may show loss or slowing of fibres but complementary studies of axonal excitability have become increasingly useful in the understanding of dysfunction of nerve fibres that are still able to conduct action potentials. These methods use threshold tracking to assess changes in membrane potential and thus gain insight into ion-channel functions. By combining different conditioning potential changes, the accommodation associated with activation of ion-channels localized at the node of Ranvier and at the internode can be assessed. BACK TO PROGRAM 10 Channelopathies in muscle Werner Z’Graggen, Departments of Neurology and Neurosurgery, University Hospital, Bern, Switzerland Muscle fibers, like nerve fibers, are complex electrical organs, in which the accurate control of membrane potential, and the interplay of multiple voltage-dependent ion channels, have essential roles in normal physiological function. The number and diversity of diseases of striated muscle greatly exceeds the number of symptoms and signs by which they express themselves clinically; thus, different diseases share certain common symptoms. The typical diagnostic sequence in a patient with suspected myopathy consists of taking patient history, clinical examination, laboratory investigation and needle electromyography followed by muscle biopsy or genetic testing. Clinical and laboratory examinations provide often rather unspecific findings. Also qualitative and quantitative electromyography have a limited sensitivity to reveal the cause of myopathy or to characterize the type of channelopathy. We have developed a method of recording muscle velocity recovery cycles, with the aim of facilitating the diagnostic process in patients with suspected myopathy. A muscle action potential is followed by early and late depolarizing afterpotentials, which can be assessed by their effects on the conduction velocity of a second muscle action potential. After the refractory period, the early afterpotential gives rise to an increase in velocity (early supernormality), which is highly sensitive to the muscle resting potential. The late afterpotential is augmented by multiple conditioning stimuli and thought to reflect potassium accumulation in the t-tubules. Muscle velocity recovery cycles provide the clinical neurophysiologist with a quick and virtually painless method of obtaining information about human muscle membrane properties in vivo. Recently, the method has been used to demonstrate distinct changes in different myopathies including channelopathies. For example it has been shown, that chloride channel dysfunction causes characteristic alterations in muscle velocity recovery cycles in myotonia congenita and the myotonic dystrophies. BACK TO PROGRAM 11 Channelopathies and pain. Kristin Ørstavik, MD, PhD. Section of Clinical Neurophysiology, Department of Neurology, Oslo University Hospital Ion-channels are crucial for conveying pain sensation in the peripheral and central nervous system. In later years the research regarding the role of ion-channels in chronic pain has been intensified. Our knowledge of possible mechanisms for neuropathic pain has been broadened due to the discovery of certain hereditary sodium-channel mutations that leads to rare chronic pain conditions such as primary erythromelalgia, while other mutations leads to an insensitivity for pain. Even in some patients with presumed idiopathic polyneuropathy, mutations of sodium-channels with a possible critical role in the generation and conduction of action potentials in nociceptors have been reported. In primary erythromelalgia patients, multiple different mutations have been identified in the gene coding for the voltage gated sodium channel subtype 1.7 (Nav1.7). Experimental animal studies have among other findings shown that this leads to hyperexcitability of nociceptors. Direct microneurographic recordings from small nerve- fibers has enabled us to study axonal properties of nociceptors in healthy subjects and how these may change in patients with painful disorders. Cnociceptors in healthy humans show a characteristic activity-dependent slowing of conduction velocity. The observation of a changed pattern of such activity-dependant slowing could reflect one aspect of the underlying ion-channel pathology in primary erythromelalgia. The analyses of mechanisms in such rare disorders might help us understand more about pathological pain including the role of ion-channel pathology. BACK TO PROGRAM 12 SFEMG - historical landmarks and present developments Erik Stålberg, Dept Clin Neurophysiology, University Hospital Uppsala Sweden In late 50ties Ekstedt and myself started at the Department of Pharmacology Uppsala University for a PhD thesis and the topic given to us was on muscle fatigue. We started with strain gauges, integrated surface EMG recordings, ischemia and so on. In order to get more information from the muscle we looked for other electrophysiological recording parameters and were inspired by Buchthal´s multielectrode. We used some of those, but thought that smaller recording surfaces perhaps could reveal more details. After lots of testing, SFEMG electrodes were constructed by ourselves containing 1-14 very small recording surfaces, each with a size smaller than the muscle fiber. The obtained signals caused considerable headache. Which is the generator, can it be just ONE muscle fiber? This was against the prevailing concept of organization of muscle fibers within the motor unit (MU) in small bundles of fibers of 10-30 fibers, a subunit. We tested to see if our signals were generated by many or just one muscle fiber by using small multielectrodes to study volume conduction, injected sodium citrate intramuscularly to activate individual muscle fibers, induced slight curarization that supposedly should have caused a disintegration of the signal if composed of many fibers, and made recordings in MG, where single fiber signals should block together in an all-or-none fashion. The conclusion after some years, that included a couple of consultations with Buchthal in Copenhagen who was our primary opponent, was that the signals really come from individual fibers.1 Another conclusion was that the organization of muscle fibers in a MU are arranged randomly, across the MU territory. During this work two separate phenomena were described. First the jitter phenomenon, which is a variability in transmission time in individual motor endplates. Its physiology was supported by intracellular recording by Elmquist and Quastel. The jitter phenomenon was closely studied both with voluntary and electrical stimulation regarding physiology (the effect of temperature, long term activity, response to drugs, ischemia, anesthetic agents) and methods for quantitation. After some time the jitter was introduced as a routine method more or less universally for the diagnosis of MG. The other parameter of the single muscle fiber was its propagation velocity.2 This varied from one discharge to the other depending on activity during the immediately preceding 1000 ms. This variability was due to the “velocity recovery function” (VRF), which followed a very strict mathematical law and was interpreted to be an ion channel phenomenon. This has recently been taken up for further excitability studies by Bostok et al. In addition the velocity decreased during continuous activity. With SFEMG recordings we also looked at the local organization of muscle fibers in a given MU, called “Fiber Density” (FD). This is abnormal in reinnervation but also in some myopathies. During the development and later clinical implementation of SFEMG, computer techniques have been essential for practical application of jitter analysis, which actually was the first application of computers in EMG. Initially we had a film camera in front of a time interval counter showing numbers, and each sweep triggered a frame in the camera. All data were then inserted manually on punch cards, which were processed in the university computer, (IBM 1640, 16 Kb). Later, time measurements were made with PCs, and today all EMG manufacturers have implemented software for jitter analysis. Over the years a number of nerve-muscle disorders have been explored with SFEMG3 and many observations have explained what we see in conventional EMG (jitter, VRF, change in propagation velocity with fatigue). With more strict rules regarding the use of disposable material in medicine, including EMG electrodes in some countries, we have been forced to find a replacement for the SFEMG electrode to measure jitter. After practical and theoretical testing we have found the smallest available “facial” concentric needle electrode to be a workable alternative for jitter measurements, but not for fiber density. A multicenter study to obtain new reference values has just been completed. The jitter is somewhat lower in this reference material than the previously developed reference limits for SFEMG, however the diagnostic sensitivity for MG has been shown to be similar to that of SFEMG. SFEMG has also been applied to study not only neuromuscular transmission but also the jitter in single anterior horn cells in vivo (via the H-reflex), F-responses, multisynaptic reflexes (blink & flexion 13 reflexes) and central transmission during cortical stimulation. A phenomenon called the “axon reflex” has been used to study the terminal motor nerve branches using electrical stimulation. The so-called “Complex Repetitive Discharges” (CRD) have been explained from SFEMG studies as a sign of hyperexcitability with ephaptic transmission between muscle fibers. In summary, jitter measured by SFEMG is an established clinical technique, which so far is the most sensitive electrophysiological parameter to detect disturbed n-m transmission in vivo. It should be stressed, however, that increased jitter is a sign of disturbed transmission at the neuromuscular junction, which is not specific for MG, since jitter is seen in early reinnervation, during ischemia, and probably during electrolyte disturbances and other conditions. SFEMG has also helped understand a number of phenomena seen in conventional EMG and is a valuable tool to study single cell activity elsewhere than in the muscle fiber. Improved technical facilities in EMG equipment have made the technical part easier, but SFEMG still requires special skill of the operator. Reference List 1. Ekstedt, J. and Stålberg, E. A method of recording extracellular action potentials of single muscle fibres and measuring their propagation velocity in voluntarily activated human muscle. Abstracts of Communications , 82-84. 1963. 2. Stålberg E. Propagation velocity in single human muscle fibres. Acta Physiologica Scandinavica 1966; suppl 287:1-112. 3. 2010. Stålberg E, Trontelj JV, Sanders DB. Single Fiber EMG. Uppsala: Edshagen Publishing House; BACK TO PROGRAM 14 Critical illness myopathy / Critical illness polyneuropathy: pathophysiology and diagnostic procedures during early course and follow up Susanne Koch, Department of Anesthesiology and Intensive Care Medicine, Charité Campus VirchowKlinikum, Berlin Objective: Neuromuscular dysfunction in critically ill patients is attributed to either critical illness myopathy (CIM) or critical illness polyneuropathy (CIP). We investigated the impact of early, electrophysiological, differential diagnostic on clinical prognosis. Immobilization, systemic inflammation and impaired glucose metabolism are major risk factors, but the underlying pathophysiology is uncertain. Methods: Critical ill patients (Sequential Organ Failure Assessment score > 8 on 3 consecutive days within 5 days in ICU) were investigated: Elektrophysiological studies including direct muscle stimulation and threshold tracking; successive muscle biopsies to assess histology, glucose metabolism and inflammation response. Unilateral electrical muscle stimulation was performed. Main Results: CIM is more frequent; CIP protracts ICU discharge and hampers complete recovery. Nonexcitable muscle membrane predicts muscle weakness, showing preferential type II fiber atrophy. Decreased synthesis and increased degradation of myosin heavy chain was found in CIM. Failing Glucose transporter-4 (GLUT-4) translocation to the sarcolemmal membrane has been proved in CIM and cannot be aboslished by insulin treatment, whereas electrical muscle stimulation increased repositioning of GLUT-4. Interestingly, skeletal muscle contributes to general inflammation, showing up-regulated serum amyloid A1 expression. Membrane depolarization of motor nerves is a general feature of critically ill patients, whereas CIM/CIP patients show reduced membrane excitability and a “paradoxical” reduced potassium current over the membrane. Conclusion: Our studies shed light on the pathophysiology of CIM / CIP, describing the central role of membrane inexcitability, immobilization, glucose metabolism and systemic inflammation. BACK TO PROGRAM 15 Bench to Bedside Project on the Intensive Care Unit Muscle wasting: Underlying Mechanisms and Specific Interventions Lars Larsson ([email protected]), Department of Physiology and Pharmacology, Department of Neuroscience, Clinical Neurophysiology, Karolinska Institutet, Stockholm, Sweden Objective. Impaired muscle function accompanies intensive care unit (ICU) patients with negative consequences for recovery from primary disease and weaning from the respirator. Accordingly, there is urgent demand for novel treatments and preventive measures, requiring research on the underlying mechanisms. This project is focused on the acquired critical illness myopathy (CIM) and the ventilator induced diaphragm muscle dysfunction (VIDD). Novel experimental models and methods for analyses of muscle tissue have been used, giving us an unprecedented opportunity to (a) address the causative factors and underlying mechanisms, and (b) develop effective treatments. Methods. Novel experimental ICU (ExICU) models together with analyses of muscle tissue from ICU patients have been used to study the mechanisms underlying the muscle wasting and impaired function of limb, respiratory and craniofacial muscles in time-resolved studies. Gene/protein expression, protein-protein interactions, mitochondria structure/function and regulation of muscle contraction at the muscle fiber level have been analyzed. Results. Long-term exposure to immobilization and mechanical ventilation in the rat ExICU model induced an identical muscle geno/phenotype as in ICU patients with CIM, suggesting that the complete mechanical silencing unique for ICU patients is an important factor underlying CIM. Mild passive mechanical loading reduced the decrease in muscle fiber function in both experimental and clinical studies, supporting early physical therapy in immobilized and mechanically ventilated ICU patients. Pharmacological intervention with a chaperone co-inducer had strong positive effects on mitochondria and muscle fiber function in the diaphragm, providing proof-of-concept for the translation of this intervention to clinical studies. Conclusion. Specific mechanisms and muscle type specific differences have been unravelled and positive outcomes of specific interventions have been documented. This will facilitate the translation of laboratory findings into practical clinical knowledge; leading to useful therapies and improved outcomes for patients in need of mechanical ventilation and critical care.We have studied the combined effects of controlled mechanical ventilation (CMV) and ageing on diaphragm muscle single fibres using a unique rat model simulating Intensive Care Unit (ICU) conditions and the effects of chaperone co-inducer (BGP-15). Methods: The effects of 5 days CMV on diaphragm muscle fibre size and function were investigated in young and old F344 Brown Norway hybrid rats. The experimental groups were deeply sedated, pharmacologically paralyzed and extensively monitored 24 hours per day. BGP-15 was given in systemically by intravenous infusion. After 5 days, the mid-costal parts of the diaphragm were dissected, chemically skinned and prepared for contractile measurements. Cross sectional area (CSA) absolute force (P0) and specific force (absolute force/CSA) were measured at the single muscle fibre level. Results: An ageing-related hypertrophy and decline in specific force were observed in control fibres. A compensatory hypertrophy was observed in response to 5 days CMV in both young and old animals. Systemic administration BGP-15 had a significant positive effect on diaphragm muscle fibre specific force in the young, restoring it to control values, but not in the old. The strong effect of BGP-15 on muscle fibre function in the young was paralleled by a significant up-regulation of HSP 70, but this effect was absent in the old. Conclusions: Significant age-specific differences were observed in control diaphragm fibres and in the response to 5 days CMV. Further, BGP-15 had a strong positive effect on diaphragm muscle fibre function and HSP expression after 5 days CMV, but this effect was restricted to the young animals. BACK TO PROGRAM 16 Optimizing testing methods and collection of reference data for differentiating critical illness polyneuropathy from critical illness myopathy Humberto Skott, MD, Karolinska Universitetssjukhuset, Huddinge, Neurofysologiska Kliniken C1-78 141 86 Stockholm, Sweden INTRODUCTION: Acquired muscle weakness in critically ill patients in the ICU is a major cause of morbidity and mortality. In severe acute quadriplegic myopathy, muscle fibers are electrically inexcitable; in critical illness polyneuropathy the excitability remains normal. Conventional electrodiagnostic methods do not provide the means to adequately differentiate these. OBJECTIVE: To further optimize methodology for the study of critically ill ICU patients and to create a reference value database in healthy controls. METHODS: Different electrophysiologic protocols were tested to find techniques as robust as possible and with sufficiently reproducible results for clinical diagnostic applications. RESULTS: Many parameters show large test - retest variability within the same healthy subject. Reference values have been collected and described as a basis for studies of weakness in critical illness. DISCUSSION: With these parameters described and quantified, we can now apply these to actual patients with weakness in the setting of critical illness. BACK TO PROGRAM 17 IOM in glioma surgery Hans Axelson The main goal of glioma surgery is to achieve maximal cytoreduction while obtaining optimal functional outcome. For this purpose, there is an increasing demand for intraoperative neurophysiology (ION) in addition to other assistive pre- and intraoperative technologies. Like any other diagnostic tool, ION may produce false positive “alarms”, with the risk of reducing the extent of resection and long-term survival. On the other hand, false negative results may instill a false sense of security which may lead to permanent neurological deficits from the surgery. Obviously, all attempt should be made to use standardized ION techniques while bearing in mind the lack of “high-evidence” support for some of the procedures. In this presentation, I will describe some of the established ION methods used in glioma surgery and share some of our experience in this context. Basically, the ION procedures are divided into mapping and monitoring techniques. Cortical mapping is the first step where the neurophysiologist aid the surgeon to find a suitable cortical entry point for tumour resection by excluding that “eloquent” cortical areas is in the harm’s way. For tumours near the primary motor cortex it may be sufficient to establish the location of the central sulcus by phase-reversal SEP whereas planned surgery near or within cortical language regions requires electrical stimulation of those regions in the awake patient. As tumour resection proceeds, it is important to continuously control the integrity of cortical areas and their subcortical projections with for instance MEP monitoring from contralateral muscles. In the awake patient, the functional status is typically monitored by clinical motor-, language- or cognitive tests in addition to some of the standard ION monitor procedures. Not to forget, is that subcortical pathways can be located by electrical stimulation in the resection cavity (subcortical mapping) which may produce a “no-go” result for further resection. BACK TO PROGRAM 18 IOM in brainstem surgery: Pål Gunnar Larsson, Dr. philos., Seksjonsleder Klinisk nevrofysiologi, Nevrokirurgisk avdeling, Oslo Universitetssykehus The human brainstem is very complex and this makes neurosurgery in the area difficult. Due to the compact nature and the complex organization it may be difficult for the neurosurgeon to navigate and to avoid damage to the locale structures. To monitor and to help localizing structures, a set of clinical neurophysiological methods are available. The cranial nerves leave the central nervous system in the brainstem area. Except the Olifactory Nerve, there are clinically available methods for monitoring all cranial nerves. The optical nerves may be monitored by continuous flash-VEP and acoustical nerve by AER. The other cranial nerves may be monitored by means of spontaneous EMG recording, and most of them may also be localized by stimulation procedures e.g. needed when the nerve roots are embedded in tumor tissue. Passing nerve tracts may be monitored both by SEP, MEP and direct stimulations. MEP may even be used on the cranial nerves, but there are challenges. Available methods and challenges will be discussed and practical experiences will be conveyed. BACK TO PROGRAM 19 Intraoperative neurophysiology in intraspinal surgery Jonas Persson, [email protected] During surgical procedures in the spinal canal there is a potential risk for damage to the spinal cord or nerve roots which could result in postoperative neurologic dysfunction. To prevent or minimize this hazard, various electrophysiological techniques are used intraoperatively. For monitoring of spinal cord motor function, motor evoked potentials (MEPs) are generated by transcranial electrical stimulation over the motor cortex and recorded from appropriate muscles (muscle MEPs, mMEPs) or asynaptically from the corticospinal tracts (direct wave, D-wave). Recording of mMEPs are often used in combination with D-wave recording to enable a graded evaluation of the motor function integrity. To evaluate the functional integrity of the lemniscal sensory pathway, which is of outermost importance in spinal cord surgery during e.g. posterior myelotomy, somatosensory evoked potentials (SEPs) are recorded transcranially over the sensory cortex following electrical stimulation of peripheral nerves (tibial nerves most often used in lower limbs and median or ulnar nerves in upper limbs). If the dorsal median raphé of the spinal cord is difficult to identify by anatomical landmarks, SEPs from the lower limbs can be recorded selectivley from the gracile fasciuli for identification of the physiological dorsal midline of the spinal cord. In addition to spinal cord surgery there are surgical procedures in the spinal canal at the level of conus medullaris/cauda equina where electrophysiological monitoring and mapping can be used. Recording of free-running EMG during surgical manipulation and recording of compound muscle action potentials (CMAPs) during fokal electrical stimulation of various structures in the operative field are done from relevant myotomes for identification of nerve root elements. Monitoring of genitourinary and anorectal functions (by e.g. pudendal SEPs, bulbocavernosus reflex) could also be of importance during surgery in this area. References: Vodušek D.B. and Deletis V. (2008) Sacral roots and nerves, and monitoring for neuro-urologic procedures. In: Handbook of Clinical Neurophysiology. Volume 8, Intraoperative Monitoring of Neural Function. M.R. Nuwer, ed. Elsevier, Amsterdam, pp. 423-433. Sala F. and Kothbauer K.F. (2008) Intraoperative neurophysiological monitoring during surgery for intramedullary spinal cord tumors. In: Handbook of Clinical Neurophysiology. Volume 8, Intraoperative Monitoring of Neural Function. M.R. Nuwer, ed. Elsevier, Amsterdam, pp. 632-650. Husain A.M. (2008) Surgery for thethered cord syndrome and other cauda equina lesions. In: Handbook of Clinical Neurophysiology. Volume 8, Intraoperative Monitoring of Neural Function. M.R. Nuwer, ed. Elsevier, Amsterdam, pp. 689-699. Rodi Z and Vodušek D.B. (2008) Monitoring of neural structures involved in micturition and sexual function. In: Handbook of Clinical Neurophysiology. Volume 8, Intraoperative Monitoring of Neural Function. M.R. Nuwer, ed. Elsevier, Amsterdam, pp. 739-747. BACK TO PROGRAM 20 Intraoperative Monitoring of Scoliosis Surgery Ralf Peter Michler,St.Olavs Hospital Trondheim The Scoliosis Research Society defines scoliosis as a lateral deviation of the normal vertical line of the spine by at least 10 degrees. There are three categories; congenital, neuromuscular and idiopathic scoliosis. The most commen, form idiopathic scoliosis, is present in 2% to 4% of children older than 10 years. Surgical intervention is indicated in patients where the curvature is over 40-50 degree. Neurologic impairment, particularly paraparesis or paraplegia are infrequent but potentially devasting complications of scoliosis surgery. The survey of 7885 scoliosis surgeries showed that spinal cord injurie occurred with a frequency of 0,72%. ( Scoliosis research society 1975). The greatest risk of spinal cord injury occurs during distraction of the spine, and injury may result from excessive elongation of the spinal cord by curve correction or by ischemic injury of the anterior spinal artery or its feeding radicular vessels, causing spinal cord ischemia. Possible factors associated with higher risk of neurological complications of scoliosis surgery are congenital scoliosis,scoliosis combined with hyperkyphosis, severity of the curve (Cobb angle over 90 degree),patients with congenital scoliosis,neuromuscular scoliosis, combined approach and decreased spinal cord perfusion due to hypotension and haemorrhage. The “ wake up” test was the first method to control the integrity of the motor tract in spinal surgery but with many limitations. The “wake up” test gives only information of spinal cord function at a single point in time, and the reversal of anesthesia confers other risks. From the 1970s somatosensory evoked potential monitoring ( SEP) has been used and a large multicenter survey by Nuwer in 1995 affirmed the efficacy of SEP monitoring in prevention of neurologic deficits. Since SEPs only monitor the neural conduction through the dorsal columns, false negative measurements happened and patients woke up paraplegic despite the absence of an intraoperative SEP signal change. In the 1990s Deletis , Epstein and colleagues introduced motoric transcranial electrical stimulation monitoring ( MEP) to intramedullary spinal cord tumor surgery. MEP was soon adopted in scoliosis surgery, and numerous studies have confirmed its efficacy. MEP monitoring is more directly relevant for detecting motor pathway injury ,and MEP deterioration often occurs before and sometimes, without SEP change ( Mac Donald et al 2007). Neverless, congruent MEP/SEP deterioration increases diagnostic certainty and suggests a more severe transverse cord compromise. In addition, reversible SEP deterioration without MEP change has been reported and implies selective dorsal column compromise ( Tome-Bermejo et al 2014,Mac Donald 2007) There is a critical window for intervention. Significant alteration of SEP and MEP signal, and recovery within 15 min. are usually not associated with postoperative deficits. ( Nuwer et al 2008). The anesthesiologist and surgeons are able to intervente in a variety of ways when IOM raises warnings: Elevating of the mean blood pressure to > 90mm Hg, increasing the oxygen concentration, measuring arterial blood gas for metabolic abnormality or low hemoglobin, irrigating the wound with warm saline solution, discontinuing spinal instrumentation,removing or adjusting grafts and hardware, and if the evoked potentials fail to return,perform a wake up test. There is general consensus in SEP intraoperative interpretation. A decrement in amplitude over 50 % is used as a warning criterion. Over 10 % increment in latency is also used as a warning criterion, but latency changes are quite common and less significant. Different warning criteria have been proposed in MEP interpretation, ranging from changes in thresholds that elicit muscle MEPs, amplitude variation, or simply the presence or absence of responses. Presence of MEPs excludes paralysis, and disappearance is a strong predictor of new weakness, with few false postives. Disappearance is a major criterion, mandating restorative efforts. Marked amplitude reduction could be a moderate criterion prompting restorative efforts, but may increase false positives. ( MacDonald 2014) 21 The D waves are generated by direct activation of the axon of fast conducting fibres of the corticospinal tract. Combined recording of D wave and muscle MEPs is a powerfull tool in spinal cord tumor surgery .The D wave amplitude remaining above 50% of baseline appears to predict long-term recovery of any early weakness, whereas irreversible over 50% reduction correlates with permanent motor deficit. In scoliosis surgery the amplitude changes up to 70% ( Ulkatan et al.,2006). This might be due to alterations of the distance between the spinal cord and the epidural recording electrode. Therfore, there is no established criterion for scoliosis surgery. Because of the high incidence of false positive results, the D wave is not very useful in IOM in scoliosis surgery. To assess thoracic pedicle screw placement, testing of the pedicle screws may be performed. Triggered thresholds below 6 mA should alert the surgeon to suspect a medial or inferior wall breach. IOM does not eliminate all adverse neurologic events. Some neurological deficits can occur despite interventions in response to the warning, because there is nothing that can be done, such as acute anterior spinal artery thrombosis. Monitoring only determines the spinal cord function at the moment of monitoring and delayed postoperative paraplegia which is often correlated with hypotension, can occur many hours after operation . Close postoperative observation is important. Successful monitoring during scoliosis surgery requires good communication between the neurophysiologist and the anesthesiologist. Neuromuscular blocking agents depress MEP and should not be used. Inhalational anesthetics interfere particulary with MEPs and should be avoided. Total intravenous anesthestics like propofol and opiate attenuate MEPs to a much lesser degree and should be preferred. It is recommened that the responsible person on the monitoring side should be an medical doctor with subspecialty education in clinical neurophysiology and additional education on intraoperative monitoring. ( Sutter et al 2007). Reliance on computerized information, without validation by trained and experienced monitoring professional can be dangerous. ( Yingling 2011) Conclusion: Optimal intraoperative monitoring during scoliosis surgery entails both SEP and MEP recording. Combination of SEP and MEP monitoring provides assessment of entire spinal cord functionality in real time. There is strong evidence that multimodality intraoperative neuromonitorering is sensitive and specific for detecting intraoperative neurologic injury during scoliosis surgery. IOM is a valuable tool to optimization of outcome in scoliosis surgery. Multimodal IOM is the Gold Standard in scoliosis surgery. References Nuwer MR.Intraoperative monitoring of neural function.Amsterdam:Elseviere;2008 Burke D,Nuwer MR;Daube J et al Intraoperative monitoring.The International Federation of Clinical Neurophysiology.Electroenceph.Clin Neurophysiolo Suppl 52:133-148 Deletis V,Sala F.Intraoperative neurophysiological monitoring of the spinal cord during spinal cord and spine surgery:a review focus on the corticospinal tracts.Clin Neurophysiol.2008;119(2):248-64 Diab M, Smith AR, Kuklo TR. The spinal Deformity Study Group et al Neural complications in the surgical treatment of adolescent idiopathic scoliosis. Spine 2007;32:2759-2763 Delank KS,Delank HW,Kong DP et al.Iatrogenic paraplegia in spinal surgery.Arch Orthop Trauma 22 Surg 125:33-41 Mendriatta A,Emerson RG.Neurophysiologic intraoperative monitoring of scoliosis surgery. J Clin.Neurophysiol 2009;26:62-69 Pastorelli F, Di Silvestre M, Plasmati R et al.The prevention of neural complications in the surgical treatment of scoliosis: the role of the neurophysiological intraoperative monitoring. Eur Spine J 2011;20 (Suppl 1):105-114 Nuwer MR, Dawson EG, Carlon LG, et al. Somatosensory evoked potential spinal cord monitoring reduces neurologic deficits after scoliosis surgery:results of a large multicenter survey. Electroencephalogr Clin Neurophysiol 1995;96;1:6-11 Pelosi L, Lamb J, Grevitt M, et al. Combined monitoring of motor and somatosensory evoked potentials in orthopaedic spinal surgery. Clin Neurophysiol 2002;113:1082-1091 MacDonald DB, Al Zayed Z. Stingsby B. Monitoring scoliosis surgery with combined multiple pulse transcranial electric motor and cortical somatosensory evoked potentials from the lower and upper extremities. Spine 2003;28:194-203 Schwartz DM, Auerbach JD, Dormans JP et al. Neurphysiological detection of impending spinal cord injury during scoliosis surgery. J Bone Joint Surg Am 2007 89 :2440-9. Eggspühler A, Sutter M, Grob D et al.Multimodal intraoperative monitoring during surgery of spinal deformities on 217 patients.Eur spine J 2007;(suppl):188-96 Sutter M, Deletis V, Dvorak J, et al. Current opinions and recommendations on multimodal intraoperative monitoring during spine surgeries Eur Spine J16 2007; (Suppl 2):232-S237 Deletis V.Intraoperative neurophysiology and methodologies used to monitor the functional integrity of the motor system.In:Deletis V,Shils JL,editors.Neurophysiology in neurosurgery.CA:Academic;2002:2551 Fehlings MG,Brodke DS,Norvell DC et al. The evidence for intraoperative neurophysiological monitorering in spine surgery:does it make a different? Spine 2010;35:37-46 Szelenyi A,Kothbauer KF,Deletis V.Transcranial electric stimulation for intraoperative motor evoked potential monitoring:Stimulation parameters and electrode montages: Clin Neurophysiol.2007,118:1586-95 Balzer JR,Crammond D,Habeych M,et al.Intraoperative EMG during spinal pedicle screw instrumentation,I:Intraoperative monitoring of neural function Handbook of Clinical Neurophysiology:Elseviere,2008;Vol8:404-42 Devlin JD,Schwartz DM..Intraoperative neurophysiologic monitoring during spinal surgery Jam Acad Orthop Surg 2007;15:549-560 Deletis V,Kothbauer K. Intraoperative Neurophysiology of the corticospinal tract inE.Stalberg,H.S.Sharma and Y.Olsson (Eds),Spinal Cord monitoring. Springer,Vienna,1998;421-444 Ginsburg HH,Shetter AG,Raudzens PA.Postoperative paraplegia with preserved intraoperative somatosensory evoked potentials.J Neurosurg 1985;63:296-300 Jones SJ,Harrison R,Koh KF et al.Motor evoked potentials monitoring during spinal surgery:responses of distal limb muscles to transcranial cortical stimulation with pulse trains.Elektroenceph Clin Neurophysiol 1996;100:375-83 23 Kothbauer K,Deletis V,Epstein F.Motor evoked potential monitoring for intramedullary spinal cord tumor surgery:correlation of clinical and neurophysiological data in a series of 100 consecutive procedures.Neurosurg.Focus 1998;4(5):1-9 Ulkatan S,Neuwirth M,Bitan F et al.Monitoring of scoliosis surgery with epidurally recorded motor evoked potentials ( D wave) revealed false results.Clin Neurophysiol.2006;2093-101 Tome-BermejoF,GarridoE,Glasby M et al.Rare true-positive isolated SSEP loss with preservation of MEPs response during scoliosis correction.Spine 2014 ;39:60-3 Mac Donald DB,Zayed ZA,Saddiq A.Four-limb muscle motor evoked potential and optimized somatosensory evoked potential monitoring with decussation assessment:results in 206 thoracolumbar spine surgeries.Eur Spine 2007;16:171-187 Taylor BA,Webb PJ,Hetreed M et al.Delayed postoperative paraplegia with hypotension in adult revision scoliosis surgery.Spine 1994;19(4):470-4 Yingling CD.Are there false-negative and false-positive motor-evoked potentials? J Clin Neurophysiolo 2011,28:607-610 Sloan TO,Heyer EJ.Anesthesia for intraoperative neurophysiologic monitoring of the spinal cord. J Neurosurg 96:430-443 BACK TO PROGRAM 24 What can you see on Neuromuscular Imaging? Michel Court-Payen, MD, PhD, Department of Musculoskeletal Radiology, GHP Gildhøj Private Hospital Copenhagen, Brøndby, Denmark Charlotte Denonville de la Cour, MD, Department of Neurophysiology, Rigshospitalet, University of Copenhagen, Denmark Ultrasound (US) is increasingly used for morphologic assessment of patients with nerve diseases as a complement to neurophysiological examination. Compared to MRI, US has following advantages: providing images with high resolution, multiregional (possible tracing of a long segment of a nerve, detection of polyneuropathy), interactive (with the clinical examination), comparative (quick examination of both sides), dynamic (nerve snapping at the elbow, US-guided needle aspiration or injection, needle biopsy, placement of EMG-needle), minimal artifacts from metal. In contrary to US, MRI provides visualization of nerves/muscles hidden by bony structures and detection of diffuse tissue edema. MRI is also better to detect small deep-situated nerves, and gives a better overview of large muscle groups. The normal fascicular structure of nerves is well demonstrated on US. US can provide localization and direct visualization of nerve entrapment with nerve flattening at the site of compression, proximal (and sometimes distal) nerve swelling, nerve hyperemia (color Doppler examination). The cause of nerve entrapment can be established (retinaculum, fibrous band, tenosynovitis, bone, osteosynthesis, tumor, cyst, or anomalous muscle). Maximal nerve swelling can be measured (nerve area). Muscle atrophy and/or fat degeneration, secondary to nerve entrapment, can be demonstrated and may be the only finding in entrapment of very small nerves. Early muscle edema is not well demonstrated with US, but easy to see on MRI. US may also be useful in patients with blunt or open trauma for detection of nerve transsection, neuroma and other lesions in the tendons and muscles. US may help detecting soft tissue tumors compressing nerves, arising from nerves (schwanomas), or ganglion cysts invading nerves (peroneal or tibial). MRI is required in patients with suspicion of malignancy. US may have a role in primary myopathic disorders, neurogenic myopathies, inflammatory myopathies, muscle tumors, and traumatic muscle lesions. BACK TO PROGRAM 25 Nerve and muscle ultrasound in neuromuscular disorders - Experiences and results of prospective studies. Erisela Qerama Montvilas, Department of Clinical Neurophysiology, Aarhus University Hospital, Denmark This oral presentation will focus on an overview of studies on ultrasound in neuromuscular disorders and will present cases, experiences and results of recent studies conducted in our department. Since its first use in the 1950s for medical practice, ultrasound has become a sophisticated imaging modality in the hands of specialists to diagnose a broad range of clinical disorders. Ultrasound provides a fast real-time and dynamic imaging capability, less inconvenience for the patient and lower cost compared to other imaging modalities. In the last two decades, ultrasound has taken an increasing important place in the evaluation of neuromuscular disorders. Studies on carpal tunnel syndrome (CTS) (1) and on ulnar nerve entrapment (UNE) (2) at the elbow have shown that enlargement and loss of echogenicity are two consistent changes on ultrasound that can distinguish diseased nerves from normal nerves. We have conducted a study on CTS and on UNE at the elbow and will present some key results from those studies. Moreover, we bring cases and experiences from the daily routine in our department where ultrasound is used as a supplement to the electrodiagnostic tests. Ultrasound may be more sensitive than EMG at detecting fasciculations (3,4) probably because it samples a larger muscle region than needle EMG and is more tolerable than the EMG. We will present first results of an ongoing study on ultrasound of muscles especially of the tounge in patients with various neuromuscular disorders. Diseased muscle displays increased echogenicity and homogeneity, atrophy and loss of the bone shadow (3). Electrographic ultrasound (EUS) is a dynamic strain imaging technique and a promising technology to identify tissue stiffness. We will present results from an ongoing study on the value of EUS as a diagnostic tool in muscle atrophy seen in neuromuscular diseases. 1-Sonography in the diagnosis of carpal tunnel syndrome: a critical review of the literature. Beekman R, Visser LH Muscle Nerve. 2003;27(1):26 2- Ulnar neuropathy at the elbow: follow-up and prognostic factors determining outcome. Beekman R, Wokke JH, Schoemaker MC, Lee ML, Visser LH Neurology. 2004;63(9):1675. 3- Muscle ultrasound in neuromuscular disorders. Pillen S, Arts IM, Zwarts MJ Muscle Nerve. 2008;37(6):679 4-Ultrasonographic detection of fasciculations markedly increases diagnostic sensitivity of ALS. Misawa S, Noto Y, Shibuya K, Isose S, Sekiguchi Y, Nasu S, Kuwabara S Neurology. 2011 Oct;77(16):1532-7. Epub 2011 Sep 21. BACK TO PROGRAM 26 Experiences of combined electrophysiology and High Resolution Ultrasound in the examination of peripheral nerves Nils Wolfram, MD, Department of Clinical Neurophysiology, Rigshospitalet, Glostrup ([email protected]) Janus Kaufmann Lindqvist, MD, Department of Neurology, Rigshospitalet, Blegdamsvej ([email protected]) A large amount of all patients referred to EMG/ENG examination of peripheral nerves end up with an unspecified diagnosis. Furthermore, electrophysiological findings do not always fit with the patients’ medical history and/or clinical examination. To evaluate the extent to which High Resolution Ultrasound (HRUS) is contributive or non-contributive to electrophysiology in relation to final diagnosis, examinations combining electrophysiology and HRUS in 2014 were evaluated. HRUS was used as an investigative tool when: - medical history and/or clinical examination gave suspicion of other specific peripheral nerve injury as expected from electrophysiological findings alone (e.g. scar tissue, trauma, tumor) or - medical history and/or clinical examination gave suspicion of localized peripheral nerve injury despite normal or unspecified electrophysiological findings. HRUS findings were classified in different groups whether supplemental ultrasound was contributive or non-contributive to electrophysiology in relation to the final diagnosis. HRUS is able to contribute to electrophysiological examination in order to localize or reveal further information in peripheral nerve injury. A couple of examples will be shown in the lecture. BACK TO PROGRAM BACK TO PROGRAM 27 Brain basis of social interaction Riitta Hari, Department of Neuroscience and Biomedical Engineering, Aalto University, Finland [email protected] Human social interaction is everywhere, effectively shaping our brains and minds. Although social interaction is among the most complex functions humans (and their brains) perform, the interaction often appears surprisingly easy. I will advocate the view that to fully understand human brain function we ultimately should be able to study interacting people in naturalistic conditions and to collect information from two brains at the same time, ending up in “two-person neuroscience” (2PN). This approach goes beyond the commonly applied “spectator science” that assumes that humans (and their brains) are reactive and that even complex social functions can be probed by presenting complexenough stimuli that the subject just observes. However, in reality people are actively participating interactors who by their behavior dynamically affect the (social) stimuli they will receive at the next moment. I will discuss our approaches and challenges in imaging of single brains under naturalistic conditions and in imaging two brains at the same time (”hyperscanning”). For 2PN purposes, we have built a setup for simultaneous MEG-to-MEG recordings between two distant laboratories and a 2-coil fMRI for imaging two subjects in the same magnet. Analysis of the 2PN-data is still extremely challenging. Most likely, we have not yet adopted the best experimental setups. BACK TO PROGRAM 28 REM sleep Behavior Disorder: an early sleep disease marker for later neurodegeneration Poul J. Jennum, Professor, chief consultant, DMSci. Danish Center for Sleep Medicine, Department of Clinical Neurophysiology and Faculty of Health, University of Copenhagen. Glostrup Hospital, Denmark Parkinson’s disease and other alpha-synucleinopathies are some of the most disabling, mortal and common chronic and neurodegenerative disorders that affect middle age and elderly humans. Once fully developed there is only symptomatic treatment but no treatment which affect the serious disease course. Therefore early detection of alpha-synucleinopathy is imperative for potential disease modifying treatment. Idiopathic Rapid eye movement sleep Behavior Disorder (iRBD) has recently been identified as a strong and early risk factor for later development of an alpha-syn’s with a conversion rate of more than 80% in 10 years. In addition, 60-100% of alpha-synucleinopathy patients suffer from RBD. iRBD is a parasomnia, characterized by loss of the normal REM sleep skeletal muscle atonia, resulting in motor/behavioral activity during sleep in relation to dream mentation. Therefore iRBD may be an early marker in the preclinical/premotor phase for alpha-synucleinopathies which is confirmed in neuropathological studies early identification of iRBD, increased understanding of disease mechanisms and development of sensitive diagnostic measures is central for future treatment-options, neuroprotective strategies, and preventing or postponing that patients with iRBD will develop Parkinson’s disease or other alphasynucleinopathies. We have shown that specific electrophysiological polysomnographic markers characterize RBD and PD patients, including: changes in macro sleep structure (loss of wake-sleep stability, sleep transitions), sleep microstructure (e.g. sleep spindles, K-complexes), muscle tone, eye activity and autonomic activity. Further we have found that changes in sleep pattern are diagnostic for diagnosing RBD/PD as compared to controls. These findings may be important for identification of early phases of RBD/PD, understanding disease process, monitoring disease progression and improving diagnostic methods. Further the results may raise opportunity to identify candidates for disease intervention. BACK TO PROGRAM 29 Electromyographic activity in REM sleep Behaviour Disorder. Rune Frandsen Objectives Rapid eye movement (REM) sleep behaviour disorder (RBD) is characterised by dream enactment and REM sleep without atonia. The evaluation of atonia is based on visual criteria but there is a need for more objective, quantitative measurements. We aimed establish a method for determining the baseline and all other parameters in automatic quantifying submental motor activity during REM sleep. Method Analysis of electromyographic (EMG) activity of the submental muscle in polysomnographs of 35 patients with idiopathic RBD (iRBD), 31 controls and 43 Parkinson's patients. Six adjustable parameters for motor activity were defined. EMG activity was automatically detected and quantified. 648 possible combinations of parameters defining EMG activity was compared for the ability to separate RBD patients from controls. After identification of the optimal method for separating RBD from controls, the parameters were used for PD patients. Results Automatic baseline estimation improved characterisation of atonia during REM sleep. We found an optimised method for quantifying motor activity during REM sleep. The method was stable in iRBD and PD patients and can be used to differentiate RBD from controls with a sensitivity and specificity of 83%. Conclusion We developed and applied a sensitive, quantitative, automatic algorithm to evaluate loss of atonia in RBD patients. BACK TO PROGRAM 30 Prepulse inhibition is associated with attention, processing speed, and 123I-FP-CIT SPECT in Parkinson's disease. Zoetmulder M1, Biernat HB2, Nikolic M3, Korbo L2, Friberg L4, Jennum PJ5. Department of Neurology, Bispebjerg University Hospital, Copenhagen NV, Denmark Danish Center for Sleep Medicine, Department of Clinical Neurophysiology, Glostrup Hospital, Glostrup, Denmark. 1 2 Department of Neurology, Bispebjerg University Hospital, Copenhagen NV, Denmark. 3 Department of Clinical Neurophysiology, Glostrup Hospital, Glostrup, Denmark. Department of Clinical Physiology and Nuclear Medicine, Bispebjerg University Hospital, Copenhagen NV, Denmark. 4 Danish Center for Sleep Medicine, Department of Clinical Neurophysiology, Glostrup Hospital, Glostrup, Denmark. 5 BACKGROUND: Prepulse inhibition is a measure of sensorimotor gating, which reflects the ability to filter or 'gate' irrelevant information. Prepulse inhibition is dramatically altered in basal ganglia disorders associated with dysfunction in the midbrain dopaminergic system, and corresponding cognitive information processing deficits such as slowed processing speed. Parkinson's disease is characterised by the degeneration of the midbrain dopaminergic system and is associated with cognitive dysfunction, including slowed information processing. Although sensorimotor processes in Parkinson's disease have been extensively studied in relation to motor function, less is known about the potential role of sensorimotor processes in cognitive function. OBJECTIVE: We investigated the relationship between prepulse inhibition, cognition and nigrostriatal dysfunction, as measured with 123I-FP-CIT-SPECT scanning, in patients with Parkinson's disease. METHODS: 38 Parkinson patients were assessed with prepulse inhibition, neuropsychological tests, and neurological investigation. A subset of these patients underwent 123I-FP-CIT-SPECT scanning. RESULTS: Patients with a higher level of prepulse inhibition performed better on cognitive measures tapping attention and processing speed than patients with a lower level of prepulse inhibition. Furthermore, there were significant correlations between prepulse inhibition and 123I-FP-CIT uptake in the striatum. CONCLUSIONS: Our results suggest that the level of prepulse inhibition is related to the efficiency of information processing in Parkinson's disease, and to the density of dopamine transporters in the striatum. BACK TO PROGRAM 31 Sleep stability and transitions in patients with idiopathic REM sleep behavior disorder and patients with Parkinson's disease Julie, Christensen - Denmark - [email protected] Objective: Patients w ith idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) are at high risk of developing Parkinson's disease (PD). As wake/sleep-regulation is thought to involve neurons located in the brainstem and hypothalamic areas, we hypothesize that the neurodegeneration in iRBD/PD is likely to affect wake/sleep and REM/non-REM (NREM) sleep transitions. Methods: We determined the frequency of wake/sleep and REM/NREM sleep transitions and the stability of wake (W), REM and NREM sleep as measured by polysomnography (PSG) in 27 patients with PD, 23 patients with iRBD, 25 patients with periodic leg movement disorder (PLMD) and 23 controls. PD patients were divided in those with RBD and those without, and iRBD patients were divided in those with major self -reported dream enactments and those with minor. Measures were computed based on manual scorings and data-driven labeled sleep staging. Results: Measures computed rom the data-driven labeling showed significant differences. Patients with PD showed significantly lower REM stability than controls and patients with PLMD. Patients with iRBD had significantly lower REM stability compared with controls. Patients with PD and RBD showed significantly lower NREM stability and significantly more REM/NREM transitions than controls. No significant differences were found between PD with and without RBD, and between iRBD patients with and without major self -reported dream-enactments. The measures computed from the manual scorings lacked to show any significant differences. Conclusion: We conclude that W, NREM and REM stability and transitions are progressively affected in iRBD and PD, probably reflecting the successive involvement of brain stem areas from early on in the disease. Sleep stability and transitions determined by a datadriven approach could support the evaluation of iRBD and PD patients. BACK TO PROGRAM 32 The Copenhagen Longitudinal Study of Male Cognitive Aging and fMRI and EEG measures of cognitive decline SubTitle: fMRI, EEG and cognition Martin, Lauritzen - Denmark - [email protected] The Copenhagen Longitudinal Study of Male Cognitive Aging (CoLoSMA) explores how aging influences cognition and brain function in testpersons from the Metropolit 1953 Danish male birth cohort. CoLoSMA is a longitudinal study based on repeated IQ tests, and the selection of the study population is based on each person's IQ trajectory. The aim is to identify etiological factors for cognitive decline in otherw ise healthy males, and to obtain fMRI and EEG data that can be used to substantiate a decline in cognitive function in order to be able to intervene before dementia sets in. Higher cognitive functions in mammals, such as perception and cognition, are critically dependent on synchronized neocortical network activity, especially activity in the gamma range (30 – 100 Hz), which is produced by repeated discharges of fastspiking inhibitory interneurons that synchronize the activity of numerous pyramidal cells by rhythmic inhibition. The presentation will describe the design of the CoLoSMA study, review the literature on neocortical gamma oscillations in pre-MCI/MCI (MCI= mild cognitive impairment) patients, and present the data obtained so far with fMRI in this birth cohort. The fMRI data point to a disturbance in one of the brain's functional connectivity networks in a large group of males (n=100) with subclinical cognitive decline in late midlife. The alterations are similar to the pattern seen in patients with Alzheimer's disease and MCI, which suggests that physiological correlates of cognitive decline may be discovered by use of appropriate methodologies. We now seek to substantiate the abnormalities at the neuronal network level by examining evoked neocortical gamma oscillations as described in the following 2 presentations. Inclusion of test-persons from the Metropolit cohort in the EEG studies was initiated February 1, 2015 and data from these males are not included in the following talks that describes results from normal controls. BACK TO PROGRAM 33 Selective attention modulates auditory and visual steady state responses Krisztina, Benedek - Denmark - [email protected] Steady state evoked potentials (EP) are widely used in cognitive neuroscience and may be useful as predictors of cognitive decline. Cognition may be examined as rivalry for attention between two sensory stimuli. Rivalry entails competitive interactions at multiple neural sites in higher brain areas, and may provide insights into the neural bases of awareness and attention. This study examined the power spectrum of auditory steady state responses in the presence of a competing visual task. Steady state auditory or visual EPs were recorded in 15 healthy individuals in three consecutive stimulation paradigms that were presented in randomized order. First, the power of an auditory 45 Hz, amplitude-modulated (2 Hz carrier frequency) stimulation was assessed without competing inputs. Second, a visual image of a face/vase illusion was presented alternating with a grey background at a frequency range of 36 Hz. Third, the auditory and visual stimulations were presented together without special instruction as to which one to attend to. The response at the stimulus f requency w as normalized to the response within the surrounding frequencies, and SNRs and power of the evoked responses w ere measured and compared. The results demonstrate that the auditory cortical responses at 45 Hz w ere markedly decreased by a competing visual stimulus. In comparison, rivalry for attention obtained by presentation of the complex, visuo-auditory paradigm resulted in a 3 fold increase of the power of the visual stimulation at 36 Hz. Auditory evoked responses were localised around, centro-temporal and centro-frontal areas, while the peak of the 36 Hz frequency elicited visual response was localised above the parieto-occipital cortex. Our findings indicate that without a goal directed attention the competition between auditory and visual processing is mainly driven by the visual stimulus during a complex sensory input. The low gamma activity evoked by this paradigm will be applied to study the test-persons in the study of cognitive decline. BACK TO PROGRAM 34 Neurophysiological correlates of illusions: Visual perceptive network study Anna Horwitz, Nelly Richard, Krisztina Benedek, Keng Wah Pang, Miki Nikolic, Martin Lauritzen. Steady state visual evoked potentials (SSVEP) have been used widely in cognitive neuroscience, but the extent to which SSVEPs can be used to track cognitive function is unknown. The amplitude of the SSVEP response is enhanced in response to attention, working memory and in several other cognitive processes. The strongest local source of SSVEPs is located in the striate cortex and propagates by the combined activity of locally and broadly distributed sources to secondary visual cortical areas. The aim of the study was to assess variations in the SSVEPs during a visual task where the participants were shown a vaseface illusion interchanging with a grey background with a flickering rate of 2 Hz, 8Hz and 36 Hz, and the evoked activity patterns for the vase-face illusion was compared with the power and spatial distribution elicited by simple checkerboard stimulation with alternations at the same three frequencies. Our study included 20 healthy individuals, mean age 35 years. Signal to noise ratios, and EEG power of the equivalent frequencies were calculated and compared statistically between checkerboard stimulation and the complex vase-face illusory image. SSVEP amplitudes were 3-5 times larger for the complex visual task as compared to checkerboard stimulation. The localization of the maximum power of the SSVEP response varied for different stimulation frequencies: 8 Hz stimulation elicited a response with maximum corresponding to the striate cortex, while the amplitude maximum at 36 Hz stimulation frequency was measured above the subdominant parieto-occipital areas. Different areas of activation of SSVEP during various stimulation points out the involvement of higher level cognitive processing during perception of illusory images, and higher stimulation frequencies elicits activity in association cortex known to be involved in cognitive processing. We suggest that SSVEP recordings may be useful to track changes in cognitive function. BACK TO PROGRAM 35 Neocortical gamma oscillations in epilepsy Krisztina Benedek, Martin Lauritzen Neocortical gamma oscillations emerge from the precise synaptic interactions of excitatory pyramidal cells and fast spiking inhibitory interneurons, which release GABA at high rate. This presentation compares high frequency EEG activity preceding and during ictal recording of patients with idiopathic generalized epilepsy and frontal lobe seizures. We used power spectral analyses of the EEG and calculated the time-frequency cross-coherence measures of neocortical gamma oscillations to search for interictal and ictal interregional rhythmic synchrony preceding and complementing clinical seizures. During primarily generalized seizures an abrupt rise of all frequencies was seen synchronously over both hemispheres. The rise in EEG gamma oscillations was short-lasting and decreased before activity at lower frequency ranges. Although interictal gamma activity was significantly higher in this population compared to non-epileptic patient’s recordings no changes were observed prior or after their clinical event. On the contrary in cases of frontal lobe epilepsy a gradual increase of high beta and gamma band was observed prior to their clinical event. This high frequency increase coincided with a decrease of delta activity. Our data supports the hypothesis that gamma synchrony plays a key role in generating and maintaining a seizure. The increase in gamma oscillatory activity precedes clinical seizures in focal epilepsy, while it rises simultaneously with other frequencies during generalized seizures. BACK TO PROGRAM 36